Role of extracellular matrix in breast cancer development: a brief update

Jena, Manoj Kumar; Janjanam, Jagadeesh

doi:10.12688/f1000research.14133.2

Cited by 72 publications

(51 citation statements)

References 79 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The interaction of breast epithelium and stroma promotes normal breast structure and function [1]. However, adipose tissue surrounding breast tumors is no longer recognized as a passive structural element, but as a key component contributing to breast cancer progression [2,3].…”

Section: Introductionmentioning

confidence: 99%

Permanent Pro-Tumorigenic Shift in Adipose Tissue-Derived Mesenchymal Stromal Cells Induced by Breast Malignancy

Plavá

Cihova

Buríková

et al. 2020

Cells

View full text Add to dashboard Cite

During cancer progression, breast tumor cells interact with adjacent adipose tissue, which has been shown to be engaged in cancer aggressiveness. However, the tumor-directed changes in adipose tissue-resident stromal cells affected by the tumor–stroma communication are still poorly understood. The acquired changes might remain in the tissue even after tumor removal and may contribute to tumor relapse. We investigated functional properties (migratory capacity, expression and secretion profile) of mesenchymal stromal cells isolated from healthy (n = 9) and tumor-distant breast adipose tissue (n = 32). Cancer patient-derived mesenchymal stromal cells (MSCs) (MSC-CA) exhibited a significantly disarranged secretion profile and proliferation potential. Co-culture with MDA-MB-231, T47D and JIMT-1, representing different subtypes of breast cancer, was used to analyze the effect of MSCs on proliferation, invasion and tumorigenicity. The MSC-CA enhanced tumorigenicity and altered xenograft composition in immunodeficient mice. Histological analysis revealed collective cell invasion with a specific invasive front of EMT-positive tumor cells as well as invasion of cancer cells to the nerve-surrounding space. This study identifies that adipose tissue-derived mesenchymal stromal cells are primed and permanently altered by tumor presence in breast tissue and have the potential to increase tumor cell invasive ability through the activation of epithelial-to-mesenchymal transition in tumor cells.

show abstract

Section: Introductionmentioning

confidence: 99%

Permanent Pro-Tumorigenic Shift in Adipose Tissue-Derived Mesenchymal Stromal Cells Induced by Breast Malignancy

Plavá

Cihova

Buríková

et al. 2020

Cells

View full text Add to dashboard Cite

show abstract

“…In the latter case, C1 annotation was based on different gene‐expression signatures (GES), GOEA, and AR and FOXA1 IHC. Proteomics data were more effective than transcriptomics data to underscore invasion and migration in C2 through identification of numerous ECM proteins . ECM dynamics is deregulated in breast cancer.…”

Section: Discussionmentioning

confidence: 99%

iTRAQ‐Based Quantitative Proteomic Analysis Strengthens Transcriptomic Subtyping of Triple‐Negative Breast Cancer Tumors

et al. 2019

View full text Add to dashboard Cite

Heterogeneity and lack of targeted therapies represent the two main impediments to precision treatment of triple‐negative breast cancer (TNBC). Therefore, molecular subtyping and identification of therapeutic pathways are required to optimize medical care. The aim of the present study is to define robust TNBC subtypes with clinical relevance by means of proteomics and transcriptomics. As a first step, unsupervised analyses are conducted in parallel on proteomics and transcriptomics data of 83 TNBC tumors. Proteomics data unsupervised analysis did not permit separation of TNBC into different subtypes, whereas transcriptomics data are able to clearly and robustly identify three subtypes: molecular apocrine (C1), basal‐like immune‐suppressed (C2), and basal‐like immune response (C3). Supervised analysis of proteomics data are then conducted based on transcriptomics subtyping. Thirty out of 62 proteins differentially expressed between C1, C2, and C3 belonged to biological categories which characterized these TNBC clusters: luminal and androgen‐regulated proteins (C1), basal, invasion, and extracellular matrix (C2), and basal and immune response (interferon pathway and immunoglobulins) (C3). Although proteomics unsupervised analysis of TNBC tumors is unsuccessful at identifying clusters, the integrated approach is promising. Identification and measurement of 30 proteins strengthen subtyping of TNBC based on robust transcriptomics unsupervised analysis.

show abstract

“…In addition, a high activity of MMP-2 and MMP-9 has been observed in the serum and tissues of patients with breast cancer compared to healthy individuals [33,34]. Several signaling pathways, such as WNT, PI3K/AKT, MAPK, JNK, focal adhesion kinase (FAK) and Src, are activated during the remodeling of the ECM [35]. Among these kinases, the secretion and activation of MMP-2 and MMP-9 in breast cancer cell lines is dependent on the cytosolic tyrosine kinases Src [36,37,38,39], and FAK [40,41].…”

Section: Introductionmentioning

confidence: 99%

Leptin Promotes Expression of EMT-Related Transcription Factors and Invasion in a Src and FAK-Dependent Pathway in MCF10A Mammary Epithelial Cells

Olea-Flores

Zuñiga-Eulogio

Tacuba-Saavedra

et al. 2019

Cells

View full text Add to dashboard Cite

Leptin is one of the main adipokines secreted in breast tissue. Leptin promotes epithelial–mesenchymal transition (EMT), cell migration and invasion in epithelial breast cells, leading to tumor progression. Although, the molecular mechanisms that underlie these events are not fully understood, the activation of different signaling pathways appears to be essential. In this sense, the effects of leptin on the activation of kinases like Src and FAK, which regulate signaling pathways that activate the EMT program, are not completely described. Therefore, we investigated the involvement of these kinases using an in vitro model for leptin-induced EMT process in the non-tumorigenic MCF10A cell line. To this end, MCF10A cells were stimulated with leptin, and Src and FAK activation was assessed. Specific events occurring during EMT were also evaluated in the presence or absence of the kinases’ chemical inhibitors PP2 and PF-573228. For instance, we tested the expression and subcellular localization of the EMT-related transcription factors Twist and β-catenin, by western blot and immunofluorescence. We also evaluated the secretion and activation of matrix metalloproteases (MMP-2 and MMP-9) by gelatin zymography. Invasiveness properties of leptin-stimulated cells were determined by invadopodia formation assays, and by the Transwell chamber method. Our results showed that leptin promotes EMT through Src and FAK activation, which leads to the secretion and activation of MMP-2 and MMP-9, invadopodia formation and cell invasion in MCF10A cells. In conclusion, our data suggest that leptin promotes an increase in the expression levels of Twist and β-catenin, the secretion of MMP-2, MMP-9, the invadopodia formation and invasion in MCF10A cells in a Src and FAK-dependent manner.

show abstract

Role of extracellular matrix in breast cancer development: a brief update

Cited by 72 publications

References 79 publications

Permanent Pro-Tumorigenic Shift in Adipose Tissue-Derived Mesenchymal Stromal Cells Induced by Breast Malignancy

Permanent Pro-Tumorigenic Shift in Adipose Tissue-Derived Mesenchymal Stromal Cells Induced by Breast Malignancy

iTRAQ‐Based Quantitative Proteomic Analysis Strengthens Transcriptomic Subtyping of Triple‐Negative Breast Cancer Tumors

Leptin Promotes Expression of EMT-Related Transcription Factors and Invasion in a Src and FAK-Dependent Pathway in MCF10A Mammary Epithelial Cells

Contact Info

Product

Resources

About